Abstract 4409: A modular polymer platform for the delivery of cytokines is effective in the treatment of head and neck squamous cell carcinoma (HNSCC)

Abstract

Abstract Educational objective: At the conclusion of this presentation, the participants should be able to discuss the benefits of a modular polymer platform, which will improve the outcome for patients with advanced HNSCC. Objective: To evaluate the therapeutic efficacy of an immunomodulator secreting polymer platform in the treatment of HNSCC. Study Design: in vivo animal study. Setting: Academic research laboratory. Subjects and Methods: C3H/HeJ mice were injected with SCCVII/SF cells. After tumors reached 1 cm in size, animals then underwent surgery and were randomized to receive implantation of (1) no polymer; (2) plain polymer; (3) plain polymer with dendritic cells (DC) secreting the chemokine CCL21; (4) plain polymer with DC alone; and 5) plain polymer + daily CCL21 injection. Tumor size was measured until the mice were euthanized. At necropsy, the tumors were excised and weighed. Results: We were able to demonstrate that DC are viable and functionally secrete CCL21 up to 14 days in the polymer. DC-CCL21 secreting polymer effectively reduced tumor growth mice by over 16-fold (P < 0.01) as compared to control, plain polymer, and plain polymer + intratumoral CCL21 injection groups. Flow cytometry analysis revealed that there was a significant increase in CD4+ T cells, as well as a significant decrease in CD4+/CD25+ regulatory T cells in the tumor site, underlying the significant tumor regression observed. Conclusion: The major limitation for the clinical use of cytokines is the lack of an effective protocol for the sustained delivery of cytokines to the tumor milieu. We demonstrate the efficacy of a novel polymer platform in delivering DC-CCL21 to SCCA in a murine model. Our results indicate that this polymer may represent a new therapeutic modality for patients with HNSCC. Once this polymer platform is optimized we will plan for validation in the context of a prospective trial in patients with unresectable advanced or recurrent HNSCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4409. doi:1538-7445.AM2012-4409